We are exploiting the utility of C. elegans in studying conserved nutrient and stress signalling pathways. In collaboration with Iqbal Hamza's group (Univ of Maryland), we have continued to study how heme levels are sensed and regulated in animals using the C. elegans model system that provides unique advantages. During the past year, we completed a study of the heme-regulated gene number seven (HRG-7)that plays a role in inter-organ signalling and organismal heme homeostasis. In collaboration with John Hanover's group (NIDDK, NIH) and Dr. Miwa (retired), we completed a genetic study that identified novel players as well as know actors in the animals ability to detect and respond to toxins. The result of these studies was an expanded understanding of how endogenous and exogenous toxins are sensed and the trigger to activate the cascade of downstream events resulting in transcriptional activation of the genes necessary for the response.